ArticlemAbs
Elimination of tumor by CD47/PD-L1 dual-targeting fusion protein that engages innate and adaptive immune responses.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 92 citations in OpenAlex.
- A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors.Targeted oncology · 2025Trial
- Antibody-dependent cellular phagocytosis in cancer immunotherapy: research and perspectives.Journal of translational medicine · 2026Review
- Impaired Macrophage Efferocytosis: Shared Mechanisms and Therapeutic Implications in Immune-Mediated Inflammatory Diseases.Journal of inflammation research · 2026Review
- Comprehensive Analysis of SIGLEC-15 and PD-L1 Expression Identifies Distinct Prognostic Profiles in Gastric Cancer.International journal of molecular sciences · 2025Article
- Emerging Immunotherapy Targets in Early Drug Development.International journal of molecular sciences · 2025Review
- Targeted CD47 checkpoint blockade using a mesothelin-directed antibody construct for enhanced solid tumor-specific immunotherapy.Cancer immunology, immunotherapy : CII · 2025Article
- Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Oncolytic adenovirus H101 enhances the anti-tumor effects of PD-1 blockade via CD47 downregulation in tumor cells.Oncology research · 2025Article
- Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody.Scientific reports · 2024Article
- Article
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- The advances in targeting CD47/SIRPα "do not eat me" axis and their ongoing challenges as an anticancer therapy.Oncotarget · 2024Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.Cancer immunology, immunotherapy : CII · 2024Article
- The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling.Cell communication and signaling : CCS · 2024Review
- Concurrent immune checkpoint blockade for enhanced cancer immunotherapy utilizing engineered hybrid nanovesicles.Frontiers in pharmacology · 2024Article
- Design of a novel chimeric peptide via dual blockade of CD47/SIRPα and PD-1/PD-L1 for cancer immunotherapy.Science China. Life sciences · 2023Article
- The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma.Experimental hematology & oncology · 2023Review
- The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection.International journal of molecular sciences · 2023Article
- HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The host immune system generally serves as a barrier against tumor formation. Programmed death-ligand 1 (PD-L1) is a critical "don't find me" signal to the adaptive immune system, whereas CD47 transmits an anti-phagocytic signal, known as the "don't eat me" signal, to the innate immune system. These and similar immune checkpoints are often overexpressed on human tumors. Thus, dual targeting both innate and adaptive immune checkpoints would likely maximize anti-tumor therapeutic effect and elicit more durable responses. Herein, based on the variable region of atezolizumab and consensus variant 1 (CV1) monomer, we constructed a dual-targeting fusion protein targeting both CD47 and PD-L1 using "Knobs-into-holes" technology, denoted as IAB. It was effective in inducing phagocytosis of tumor cells, stimulating T-cell activation and mediating antibody-dependent cell-mediated cytotoxicity in vitro. No obvious sign of hematological toxicity was observed in mice administered IAB at a dose of 100 mg/kg, and IAB exhibited potent antitumor activity in an immune-competent mouse model of MC38. Additionally, the anti-tumor effect of IAB was impaired by anti-CD8 antibody or clodronate liposomes, which implied that both CD8+ T cells and macrophages were required for the anti-tumor efficacy of IAB and IAB plays an essential role in the engagement of innate and adaptive immune responses. Collectively, these results demonstrate the capacity of an elicited endogenous immune response against tumors and elucidate essential characteristics of synergistic innate and adaptive immune response, and indicate dual blockade of CD47 and PD-L1 by IAB may be a synergistic therapy that activates both innate and adaptive immune response against tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.